The regulation of cell-mediated immunity (CMI) is being investigated in the context of chronic infections, in general, and leprosy, in particular. A number of experimental mouse models are being examined. Some, such as vaccination with living BCG or irradiation-killed M. leprae induce a highly stable state of CMI. Conversely, subcutaneous infection with M. lepraemurium (MLM) engenders a very unstable state of CMI which is easily suppressed by systemic injection of either live, intact dead, or disrupted MLM. Similar suppression occurs spontaneously during the course of normally progressive infection. Stable states of CMI will also be specifically suppressed by systemic injections of homologous antigen. Unstable CMI will be averted or reversed by treatment with immunopotentiating agents. Preliminary evidence suggests that the suppression of CMI is mediated by sub-classes of T-lymphocytes, and these cells will be characterized by use of Lyt and I-J antisera and other cell separation techniques. These procedures will also be used to determine the identity of the cells which mediate delayed hypersensitivity, antigen-specific lymphocyte transformation, lymphokine production and protective immunity.